title: Epstein-Barr Virus latent membrane protein 1 induces Snail and epithelial-mesenchymal transition in metastatic nasopharyngeal carcinoma.
abstract: BACKGROUND
  Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) is distinctive among head-and-neck cancers in its undifferentiated histopathology and highly metastatic character. We have recently investigated the involvement of epithelial-mesenchymal transition (EMT) in NPC. In a previous study, we found a close association of expression of LMP1, the principal EBV oncoprotein, with expression of Twist and induction of EMT.
  
  
  METHODS
  We analysed expression of Snail in 41 NPC tissues by immunohistochemistry. The role of Twist as well as Snail in EMT of NPC was investigated by using NP69SV40T human nasopharyngeal cells.
  
  
  RESULTS
  In NPC tissues, overexpression of Snail is associated with expression of LMP1 in carcinomatous cells. In addition, expression of Snail positively correlated with metastasis and independently correlated inversely with expression of E-cadherin. Expression of Twist had no association with expression of E-cadherin. Further, in a human nasopharyngeal cell line, LMP1 induces EMT and its associated cellular motility and invasiveness. Expression of Snail is induced by LMP1 in these cells, and small hairpin RNA (shRNA) to Snail reversed the cellular changes. By contrast, Twist did not produce EMT in these nasopharyngeal cells.
  
  
  CONCLUSIONS
  This study strengthens the association of EMT with the metastatic behaviour of NPC. These results suggest that induction of Snail by the EBV oncoprotein LMP1 has a pivotal role in EMT in NPC.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, NC 27599-7295, USA.
authors.forename: T
authors.initials: T
authors.lastname: Horikawa
authors.forename: T
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.forename: M
authors.initials: M
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kaizaki
authors.forename: J S
authors.initials: JS
authors.lastname: Pagano
mesh_terms: D015820:Cadherins / Q000032:analysis; D002277:Carcinoma; D058750:Epithelial-Mesenchymal Transition; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000473:pathology / Q000821:virology; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: D015820:Cadherins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014763:Viral Matrix Proteins